Nausea and vomiting are a serious complication of surgery and certain areas of chemotherapy, particularly cancer treatment. Historically, dopamine receptor antagonists, such as droperidol or prochlorperazine, have been used to treat nausea and vomiting. These agents, however, tend to produce unwanted side effects such as prolactin release and sedation.
Recently, a new class of agents, characterized by their antagonism of serotonin at the 5-HT.sub.3 receptor with little or no D.sub.2 receptor antagonist properties, has been found to prevent or curtail emetic episodes caused by irradiation or chemotherapeutic agents such as cisplatin. These effects were potentiated by coadministration of dexamethasone. In addition, these 5-HT.sub.3 antagonists are useful in the treatment of gastric motility, anxiety, migraine, psychiatric disorders, and memory impairment. Various analogs of these new agents were found to have effects at a new serotonin receptor which is coupled to adenylate cyclase, and which has been called the 5HT.sub.4 receptor. Agents of this latter type are thought to be associated with promotility and, therefore, have potential utility in treating gastrointestinal dysfunctions such as reflux oesophagitis and gastric stasis.
United Kingdom patent application no. 2,158,440, discloses certain 4,5,6,7-tetrahydroimidazo[4,5-c]pyridinyl carboxylic amide derivatives useful as antiviral agents.
U.S. Pat. No. 4,977,175, issued to Ohta et al., discloses 4,5,6,7-tetrahydrobenzimidazole derivatives useful as antagonists of 5-HT.sub.3 receptors.
U.S. Pat. No. 4,963,546, issued to North et al., discloses 3-substituted indole derivatives useful as antagonists of 5-HT.sub.3 receptors.